This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the current reporting period we confirmed that anti-CD137-mediated suppression could be induced in CD8 T cells, as well as CD4 T. By adoptively transferring CD137-sufficient SMARTA transgenic CD4 T cells and CD137-sufficient P14 TCR transgenic CD8 T cells into CD137-deficient mice and we have found that the induction of suppression caused by anti-CD137 was in part dependent on CD137 expression on T cells, rather than completely independent, as we had previously reported. The contribution made by CD137 signaling to T cells was found to be the upregulation of the apoptosis-inducing death receptor CD95 (Fas). In addition, we found that CD137-mediated signaling in pDCs and mDCs was critical to the induction of tolerance of virus-specific CD8 T cells and that DCs contributed to the induction of CD8 T cell tolerance by inducing the release of soluble Fas ligand. We showed that although DCs induced the release of soluble Fas ligand, they were not the source of this protein. Our studies are presently focused on the identification of the cell lineage that is responsible for the release of Fas ligand. In other studies we have found that CD137 and its cognate ligand function as gate keepers and limit the extent of early myelopoiesis in the bone marrow, an event that limits the numbers of DCs that leave the bone marrow and enter the periphery. This approach will advance our understanding of immune response of conditions such as HIV infection.